Generation of highly potent nonviral gene vectors by complexation of lipoplexes and transferrin-bearing fusogenic polymer-modified liposomes in aqueous glucose solution.
Generation of highly potent nonviral gene vectors by complexation of lipoplexes and transferrin-bearing fusogenic polymer-modified liposomes in aqueous glucose solution.
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DOI：
10.1016/j.biomaterials.2007.11.016
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发表时间：
2008-03
期刊：
影响因子：
14
通讯作者：
Naoki Sakaguchi;C. Kojima;Atsushi Harada;Kazunori Koiwai;K. Shimizu;N. Emi;K. Kono
中科院分区：
文献类型：
--
作者：
Naoki Sakaguchi;C. Kojima;Atsushi Harada;Kazunori Koiwai;K. Shimizu;N. Emi;K. Kono
我们以前报道过，含有3，5-双十五烷氧基苯甲脒（TRX-20）和转铁蛋白的琥珀酰化聚缩水甘油（SucPG）修饰的脂质体，在弱酸性条件下成为融合复合物，可能会产生高转染活性的基因载体。对于本研究，我们通过将它们混合在磷酸盐缓冲盐水或5%葡萄糖水溶液中来制备lipoplex-SucPG修饰的脂质体复合物。在磷酸盐缓冲溶液中制备的复合物具有大于800 nm的大颗粒，而在葡萄糖溶液中制备的复合物非常小：200- 300 nm。小的复合物更有效地被HeLa细胞吸收，并且它们的转染比大的复合物更有效地诱导。此外，小的复合物实现细胞转染更有效地在血清的存在下比在血清的情况下，没有显着的细胞毒性。考虑到它们对细胞的亲和力是基于配体-受体相互作用，小复合物作为具有高转染活性和高靶细胞特异性的安全载体是非常有前途的。
We reported previously that complexation of lipoplexes containing 3,5-dipentadecyloxybenzamidine (TRX-20) and transferrin-bearing succinylated poly(glycidol) (SucPG)-modified liposome, which becomes fusogenic under weakly acidic conditions, might produce gene carriers with high transfection activity. For the present study, we prepared the lipoplex–SucPG-modified liposome complexes by mixing them either in phosphate-buffered saline or in an aqueous 5% glucose solution. The complexes prepared in phosphate-buffered saline have large particles of more than 800nm, whereas the complexes prepared in the glucose solution were remarkably small: 200–300nm. The small complexes were taken up more effectively by HeLa cells, and their transfection was induced more efficiently than the large complexes'. In addition, the small complexes achieved cellular transfection more efficiently in the presence of serum than in the absence of serum, without marked cytotoxicity. Considering that their affinity to the cell is based on ligand–receptor interaction, the small complexes are highly promising as a safe vector with high transfection activity and high target cell specificity.